In recent years, demand of a biological polymer, such as a protein, an enzyme and a nucleic acid, has been drastically increased for biopharmaceuticals. In general, biopharmaceuticals are generally produced through a cultivation step and a subsequent separation-purification step. It is therefore coveted to establish an easy purification technology in a large scale in addition to a cultivation technology for improving an expression level of a target substance.
In order to purify a protein, a chromatographic isolation method is generally used, such as ion-exchange chromatography, hydrophobic interaction chromatography, reversed-phase chromatography, gel filtration chromatography and affinity chromatography. However, it is very difficult to obtain a pure target protein using only one purification technology, since there are many kinds of proteins in a culture medium after a cultivation step. Therefore, a purification process in which several methods are used in combination is generally employed (Patent Document 1).
Recently, an antibody drug has been actively developed as a medical protein. An antibody drug means a medicinal drug which utilizes a function of an antibody. An antibody drug reduces the side effects of a conventional medical drug and is expected to have a high therapeutic effect, since the antibody drug specifically acts on a target molecule.
An antibody drug actually contributes to an improvement of various disease conditions. However, with respect to an antibody drug, it is said that the purity thereof profoundly affects the quality in comparison with other medical proteins, since the antibody drug is administered to a living body in a large amount.
In order to produce a highly pure antibody, an affinity chromatography method, in which a molecule having a property to specifically bind to the target antibody is used as a ligand, is generally used. A monoclonal IgG antibody is mainly developed as an antibody drug, and Protein A which is produced by Staphylococcus is well-known as a ligand having an affinity for an IgG antibody.
For example, in an early stage of a purifying step, i.e. capturing step, of a process for producing an antibody drug, a column for affinity chromatography in which Protein A is immobilized as a ligand on a water-insoluble base material is generally used (Non-patent Document 1 and Non-patent Document 2). Hereinafter, such a column for affinity chromatography is referred to as “Protein A column”.
However, Protein A needs a high producing cost; therefore, various technological developments are promoted to improve the properties of a column. For example, a ligand is modified in a protein engineered approach to increase an amount to be bound to a column (Patent Document 2 and Patent Document 3) and to improve an alkalinity-resistance for washing (Patent Document 4 and Patent Document 5).
On the other hand, a replacement for Protein A is developed. For example, a base material on which a synthesized low-molecular-weight compound having a property to bind to an antibody is marketed as MAbsorbent (trade mark) manufactured by ProMetic BioSciences Ltd.
As a low-molecular-weight compound which can bind to an antibody, a sulfone derivative (Patent Document 6), a triazine derivative (Patent Document 7), a mercapto heterocyclic ring compound (Patent Document 8), a 4-pyridylethylthioalkyl derivative (Non-patent Document 3) and a thiazole derivative (Patent Document 9) are well-known. The compounds are excellent in a chemical and physical stability.
However, there is fear that the above-described replacements for Protein A exhibit a non-specific adsorption depending on the basic structure thereof.